Cephalosporin cross sensitivity with penicillin. 10%?

What we have always learnt:

  • In a patient allergic to penicillin, the cross sensitivity to any cephalosporins is 10% (it means that if you use a cephalosporin in a patient allergic to penicillin, the risk of them getting allergy is 10%)
  • Is it true?

This table answers it all.

1 2

Too complicated? let’s look at the three largest retrospective studies:

Capture

  1. Patients who reported a history of penicillin allergy may not have true penicillin allergy confirmed by skin test..
    – True penicillin allergy is IgE mediated.
    – They may have IgG or IgM reaction causing vomiting, diarrhea or non specific rash.
  2. The cross allergy between penicillin and cephalosporin is around 1%.

Let’s look at this meta-analysis by  Pichichero et al.

Cross sens of penicillin and cephalosporin in patients who reported having penicllin allergy (history alone)

a

Incidence rate across all generations = 96/2387 = 4%

1

2

d

Cross sens of penicillin and cephalosporin in a patient with penicillin allergy confirmed by skin testing:

4

Incidence in (+) skin test = 8/451 = 2%

  • Likely to reflect rate of cross sens closer to reality since penicillin allergy here is confirmed to be a true IgE reaction.

4s 5 6

Why is this so?

  • Cross allergy has been implicated due to similar R1 side chain (ie, cefaclor, cefadroxil, cefatrizine, cefprozil, cephalexin,and cephradine – main first and second generation cephalosporins).

Conclusion

  • Not all patients with history of penicillin allergy has true allergy.
  • As seen above, positive skin test to penicillin does not predict response to cephalosporins (21 cases happened in negative skin test as shown in the meta-analysis)
  • True cross allergy is only 1-4%
    – And limited to only a few first and second generation cephalosporins.
    – Basically among the lists, only Keflex (cephalexin) is commonly used now for cellulitis and osteomyelitis.
  • Avoid first and second generation cephalosporins with similar side chains. First and second generation with different side chains should be used instead.
  • Third and fourth generation cephalosporins have negligible cross sens with penicillin.

e

References:

James D. Campagna, MD, Michael C. Bond, MD, Esteban Schabelman, MD, MBA, and Bryan D. Hayes, PHARMD. THE USE OF CEPHALOSPORINS IN PENICILLIN-ALLERGIC PATIENTS:A LITERATURE REVIEW. The Journal of Emergency Medicine, 2012;42(5):612-20

Michael E. Pichichero, MD, and Janet R. Casey, MD, Rochester, NY. Safe use of selected cephalosporins in
penicillin-allergic patients: A meta-analysis. Otolaryngology–Head and Neck Surgery (2007) 136, 340-347

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